Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells
At the onset of neurogenesis in the mammalian central nervous system, neuroepithelial cells switch from symmetric, proliferative to asymmetric, neurogenic divisions. In analogy to the asymmetric division of Drosophila neuroblasts, this switch of mammalian neuroepithelial cells is thought to involve...
Gespeichert in:
Veröffentlicht in: | The EMBO journal 2004-06, Vol.23 (11), p.2314-2324 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext bestellen |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 2324 |
---|---|
container_issue | 11 |
container_start_page | 2314 |
container_title | The EMBO journal |
container_volume | 23 |
creator | Kosodo, Yoichi Röper, Katja Haubensak, Wulf Marzesco, Anne-Marie Corbeil, Denis Huttner, Wieland B |
description | At the onset of neurogenesis in the mammalian central nervous system, neuroepithelial cells switch from symmetric, proliferative to asymmetric, neurogenic divisions. In analogy to the asymmetric division of
Drosophila
neuroblasts, this switch of mammalian neuroepithelial cells is thought to involve a change in cleavage plane orientation from perpendicular (vertical cleavage) to parallel (horizontal cleavage) relative to the apical surface of the neuroepithelium. Here, we report, using
TIS21
‐GFP knock‐in mouse embryos to identify neurogenic neuroepithelial cells, that at the onset as well as advanced stages of neurogenesis the vast majority of neurogenic divisions, like proliferative divisions, show vertical cleavage planes. Remarkably, however, neurogenic divisions of neuroepithelial cells, but not proliferative ones, involve an asymmetric distribution to the daughter cells of the apical plasma membrane, which constitutes only a minute fraction (1–2%) of the entire neuroepithelial cell plasma membrane. Our results support a novel concept for the cell biological basis of asymmetric, neurogenic divisions of neuroepithelial cells in the mammalian central nervous system. |
doi_str_mv | 10.1038/sj.emboj.7600223 |
format | Article |
fullrecord | <record><control><sourceid>proquest_C6C</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_419905</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>984107951</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5993-f95a85047e46d68009f21138a71f8c0eefd404702cb73865da4038e8e54a7a2a3</originalsourceid><addsrcrecordid>eNqFksFv0zAYxS0EYmVw5wKKOHBLsR07tg8ctjEG04DLEEfLTb50LrGT2cm2_ve4S9UOJLSTFb33-_z5vSD0muA5wYX8EFdzcItuNRclxpQWT9CMsBLnFAv-FM0wLUnOiFQH6EWMK4wxl4I8RweEE0ZISWdoOIpr52AItspqG9O5GAfb-axrsuEKMtPbyrRZ35roTObSbcF4yOoxWL_MPIyhW4K_h29sTGDckM44Z1pr_OSA3qZZ6bvNKmjb-BI9a0wb4dX2PEQ_P59ennzJL36cfT05usgrrlSRN4obyTETwMq6lBirhhJSSCNIIysM0NQsqZhWC1HIkteGpVBAAmdGGGqKQ_RxmtuPCwd1BX4IptV9sM6Ete6M1X8r3l7pZXejGVEK88S_3_Khux4hDtrZuHlBiqAboxZElaJIuT9mJEIJLhVLxnf_GFfdGHwKQRPFaUkJF8mEJ1MVuhgDNLuNCdab3nVc6fve9bb3hLx9-NI9sC06GdRkuLUtrB8dqE-_HZ_vh5OJjf2mdQgPlv7_Qm8mxpthDLC7cK_nk57-ObjbySb81ilSwfWv72eaHX9iDItzfVn8AYdP6G8</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>195262157</pqid></control><display><type>article</type><title>Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells</title><source>Springer Nature OA Free Journals</source><creator>Kosodo, Yoichi ; Röper, Katja ; Haubensak, Wulf ; Marzesco, Anne-Marie ; Corbeil, Denis ; Huttner, Wieland B</creator><creatorcontrib>Kosodo, Yoichi ; Röper, Katja ; Haubensak, Wulf ; Marzesco, Anne-Marie ; Corbeil, Denis ; Huttner, Wieland B</creatorcontrib><description>At the onset of neurogenesis in the mammalian central nervous system, neuroepithelial cells switch from symmetric, proliferative to asymmetric, neurogenic divisions. In analogy to the asymmetric division of
Drosophila
neuroblasts, this switch of mammalian neuroepithelial cells is thought to involve a change in cleavage plane orientation from perpendicular (vertical cleavage) to parallel (horizontal cleavage) relative to the apical surface of the neuroepithelium. Here, we report, using
TIS21
‐GFP knock‐in mouse embryos to identify neurogenic neuroepithelial cells, that at the onset as well as advanced stages of neurogenesis the vast majority of neurogenic divisions, like proliferative divisions, show vertical cleavage planes. Remarkably, however, neurogenic divisions of neuroepithelial cells, but not proliferative ones, involve an asymmetric distribution to the daughter cells of the apical plasma membrane, which constitutes only a minute fraction (1–2%) of the entire neuroepithelial cell plasma membrane. Our results support a novel concept for the cell biological basis of asymmetric, neurogenic divisions of neuroepithelial cells in the mammalian central nervous system.</description><identifier>ISSN: 0261-4189</identifier><identifier>EISSN: 1460-2075</identifier><identifier>DOI: 10.1038/sj.emboj.7600223</identifier><identifier>PMID: 15141162</identifier><identifier>CODEN: EMJODG</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; apical plasma membrane ; asymmetric division ; Cadherins - metabolism ; Cell Cycle Proteins - biosynthesis ; Cell Cycle Proteins - genetics ; Cell Division ; Cell Membrane - metabolism ; Central nervous system ; Central Nervous System - cytology ; Central Nervous System - embryology ; Central Nervous System - metabolism ; cleavage plane ; Contractile Proteins - metabolism ; DNA - metabolism ; EMBO11 ; EMBO27 ; Embryos ; Green Fluorescent Proteins - metabolism ; Heterozygote ; Mammals ; Membranes ; Mice ; Neuroepithelial Cells - metabolism ; neurogenesis ; TIS21</subject><ispartof>The EMBO journal, 2004-06, Vol.23 (11), p.2314-2324</ispartof><rights>European Molecular Biology Organization 2004</rights><rights>Copyright © 2004 European Molecular Biology Organization</rights><rights>Copyright Nature Publishing Group Jun 2, 2004</rights><rights>Copyright © 2004, European Molecular Biology Organization 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5993-f95a85047e46d68009f21138a71f8c0eefd404702cb73865da4038e8e54a7a2a3</citedby><cites>FETCH-LOGICAL-c5993-f95a85047e46d68009f21138a71f8c0eefd404702cb73865da4038e8e54a7a2a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC419905/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC419905/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,1417,1433,27924,27925,41120,42189,45574,45575,46409,46833,51576,53791,53793</link.rule.ids><linktorsrc>$$Uhttps://doi.org/10.1038/sj.emboj.7600223$$EView_record_in_Springer_Nature$$FView_record_in_$$GSpringer_Nature</linktorsrc><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15141162$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kosodo, Yoichi</creatorcontrib><creatorcontrib>Röper, Katja</creatorcontrib><creatorcontrib>Haubensak, Wulf</creatorcontrib><creatorcontrib>Marzesco, Anne-Marie</creatorcontrib><creatorcontrib>Corbeil, Denis</creatorcontrib><creatorcontrib>Huttner, Wieland B</creatorcontrib><title>Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells</title><title>The EMBO journal</title><addtitle>EMBO J</addtitle><addtitle>EMBO J</addtitle><description>At the onset of neurogenesis in the mammalian central nervous system, neuroepithelial cells switch from symmetric, proliferative to asymmetric, neurogenic divisions. In analogy to the asymmetric division of
Drosophila
neuroblasts, this switch of mammalian neuroepithelial cells is thought to involve a change in cleavage plane orientation from perpendicular (vertical cleavage) to parallel (horizontal cleavage) relative to the apical surface of the neuroepithelium. Here, we report, using
TIS21
‐GFP knock‐in mouse embryos to identify neurogenic neuroepithelial cells, that at the onset as well as advanced stages of neurogenesis the vast majority of neurogenic divisions, like proliferative divisions, show vertical cleavage planes. Remarkably, however, neurogenic divisions of neuroepithelial cells, but not proliferative ones, involve an asymmetric distribution to the daughter cells of the apical plasma membrane, which constitutes only a minute fraction (1–2%) of the entire neuroepithelial cell plasma membrane. Our results support a novel concept for the cell biological basis of asymmetric, neurogenic divisions of neuroepithelial cells in the mammalian central nervous system.</description><subject>Animals</subject><subject>apical plasma membrane</subject><subject>asymmetric division</subject><subject>Cadherins - metabolism</subject><subject>Cell Cycle Proteins - biosynthesis</subject><subject>Cell Cycle Proteins - genetics</subject><subject>Cell Division</subject><subject>Cell Membrane - metabolism</subject><subject>Central nervous system</subject><subject>Central Nervous System - cytology</subject><subject>Central Nervous System - embryology</subject><subject>Central Nervous System - metabolism</subject><subject>cleavage plane</subject><subject>Contractile Proteins - metabolism</subject><subject>DNA - metabolism</subject><subject>EMBO11</subject><subject>EMBO27</subject><subject>Embryos</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Heterozygote</subject><subject>Mammals</subject><subject>Membranes</subject><subject>Mice</subject><subject>Neuroepithelial Cells - metabolism</subject><subject>neurogenesis</subject><subject>TIS21</subject><issn>0261-4189</issn><issn>1460-2075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFksFv0zAYxS0EYmVw5wKKOHBLsR07tg8ctjEG04DLEEfLTb50LrGT2cm2_ve4S9UOJLSTFb33-_z5vSD0muA5wYX8EFdzcItuNRclxpQWT9CMsBLnFAv-FM0wLUnOiFQH6EWMK4wxl4I8RweEE0ZISWdoOIpr52AItspqG9O5GAfb-axrsuEKMtPbyrRZ35roTObSbcF4yOoxWL_MPIyhW4K_h29sTGDckM44Z1pr_OSA3qZZ6bvNKmjb-BI9a0wb4dX2PEQ_P59ennzJL36cfT05usgrrlSRN4obyTETwMq6lBirhhJSSCNIIysM0NQsqZhWC1HIkteGpVBAAmdGGGqKQ_RxmtuPCwd1BX4IptV9sM6Ete6M1X8r3l7pZXejGVEK88S_3_Khux4hDtrZuHlBiqAboxZElaJIuT9mJEIJLhVLxnf_GFfdGHwKQRPFaUkJF8mEJ1MVuhgDNLuNCdab3nVc6fve9bb3hLx9-NI9sC06GdRkuLUtrB8dqE-_HZ_vh5OJjf2mdQgPlv7_Qm8mxpthDLC7cK_nk57-ObjbySb81ilSwfWv72eaHX9iDItzfVn8AYdP6G8</recordid><startdate>20040602</startdate><enddate>20040602</enddate><creator>Kosodo, Yoichi</creator><creator>Röper, Katja</creator><creator>Haubensak, Wulf</creator><creator>Marzesco, Anne-Marie</creator><creator>Corbeil, Denis</creator><creator>Huttner, Wieland B</creator><general>John Wiley & Sons, Ltd</general><general>Nature Publishing Group UK</general><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PCBAR</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20040602</creationdate><title>Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells</title><author>Kosodo, Yoichi ; Röper, Katja ; Haubensak, Wulf ; Marzesco, Anne-Marie ; Corbeil, Denis ; Huttner, Wieland B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5993-f95a85047e46d68009f21138a71f8c0eefd404702cb73865da4038e8e54a7a2a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>apical plasma membrane</topic><topic>asymmetric division</topic><topic>Cadherins - metabolism</topic><topic>Cell Cycle Proteins - biosynthesis</topic><topic>Cell Cycle Proteins - genetics</topic><topic>Cell Division</topic><topic>Cell Membrane - metabolism</topic><topic>Central nervous system</topic><topic>Central Nervous System - cytology</topic><topic>Central Nervous System - embryology</topic><topic>Central Nervous System - metabolism</topic><topic>cleavage plane</topic><topic>Contractile Proteins - metabolism</topic><topic>DNA - metabolism</topic><topic>EMBO11</topic><topic>EMBO27</topic><topic>Embryos</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Heterozygote</topic><topic>Mammals</topic><topic>Membranes</topic><topic>Mice</topic><topic>Neuroepithelial Cells - metabolism</topic><topic>neurogenesis</topic><topic>TIS21</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kosodo, Yoichi</creatorcontrib><creatorcontrib>Röper, Katja</creatorcontrib><creatorcontrib>Haubensak, Wulf</creatorcontrib><creatorcontrib>Marzesco, Anne-Marie</creatorcontrib><creatorcontrib>Corbeil, Denis</creatorcontrib><creatorcontrib>Huttner, Wieland B</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The EMBO journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Kosodo, Yoichi</au><au>Röper, Katja</au><au>Haubensak, Wulf</au><au>Marzesco, Anne-Marie</au><au>Corbeil, Denis</au><au>Huttner, Wieland B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells</atitle><jtitle>The EMBO journal</jtitle><stitle>EMBO J</stitle><addtitle>EMBO J</addtitle><date>2004-06-02</date><risdate>2004</risdate><volume>23</volume><issue>11</issue><spage>2314</spage><epage>2324</epage><pages>2314-2324</pages><issn>0261-4189</issn><eissn>1460-2075</eissn><coden>EMJODG</coden><abstract>At the onset of neurogenesis in the mammalian central nervous system, neuroepithelial cells switch from symmetric, proliferative to asymmetric, neurogenic divisions. In analogy to the asymmetric division of
Drosophila
neuroblasts, this switch of mammalian neuroepithelial cells is thought to involve a change in cleavage plane orientation from perpendicular (vertical cleavage) to parallel (horizontal cleavage) relative to the apical surface of the neuroepithelium. Here, we report, using
TIS21
‐GFP knock‐in mouse embryos to identify neurogenic neuroepithelial cells, that at the onset as well as advanced stages of neurogenesis the vast majority of neurogenic divisions, like proliferative divisions, show vertical cleavage planes. Remarkably, however, neurogenic divisions of neuroepithelial cells, but not proliferative ones, involve an asymmetric distribution to the daughter cells of the apical plasma membrane, which constitutes only a minute fraction (1–2%) of the entire neuroepithelial cell plasma membrane. Our results support a novel concept for the cell biological basis of asymmetric, neurogenic divisions of neuroepithelial cells in the mammalian central nervous system.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>15141162</pmid><doi>10.1038/sj.emboj.7600223</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext_linktorsrc |
identifier | ISSN: 0261-4189 |
ispartof | The EMBO journal, 2004-06, Vol.23 (11), p.2314-2324 |
issn | 0261-4189 1460-2075 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_419905 |
source | Springer Nature OA Free Journals |
subjects | Animals apical plasma membrane asymmetric division Cadherins - metabolism Cell Cycle Proteins - biosynthesis Cell Cycle Proteins - genetics Cell Division Cell Membrane - metabolism Central nervous system Central Nervous System - cytology Central Nervous System - embryology Central Nervous System - metabolism cleavage plane Contractile Proteins - metabolism DNA - metabolism EMBO11 EMBO27 Embryos Green Fluorescent Proteins - metabolism Heterozygote Mammals Membranes Mice Neuroepithelial Cells - metabolism neurogenesis TIS21 |
title | Asymmetric distribution of the apical plasma membrane during neurogenic divisions of mammalian neuroepithelial cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T06%3A22%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_C6C&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Asymmetric%20distribution%20of%20the%20apical%20plasma%20membrane%20during%20neurogenic%20divisions%20of%20mammalian%20neuroepithelial%20cells&rft.jtitle=The%20EMBO%20journal&rft.au=Kosodo,%20Yoichi&rft.date=2004-06-02&rft.volume=23&rft.issue=11&rft.spage=2314&rft.epage=2324&rft.pages=2314-2324&rft.issn=0261-4189&rft.eissn=1460-2075&rft.coden=EMJODG&rft_id=info:doi/10.1038/sj.emboj.7600223&rft_dat=%3Cproquest_C6C%3E984107951%3C/proquest_C6C%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=195262157&rft_id=info:pmid/15141162&rfr_iscdi=true |